The loss of mental function associated with Alzheimer's disease could be due to the loss of nerve cells and/or a dysfunction in neurotransmission which is secondary to a change in the composition and fluidity of the neuronal membrane. The specific aim of this proposal is to purify the synaptosomal plasma membrane (SPM) from rats of various ages and to determine if there are changes in the lipid composition and/or fluidity of this neuronal plasma membrane during aging. SPM will be purified by density gradient centrifugation and carefully characterized for purity with marker enzymes and electron microscopy. The lipid composition of the membranes will be determined using standard chloroform/methanol extraction procedures in combination with thin layer chromatography. The SPM cholesterol, phospholipid and protein content will be determined with particular attention focused on possible changes in the choleterol to phospholipid molar ratio. Additional studies wil investigate the distribution of the various phospholipid classes and their fatty acid composition. The fluid properties of the membrane will be investigated using the fluorescence polarization of a fluorescent membrane probe. The apparent microviscosity of the SPM will be measured over a temperature range of 0-40 C. These studies will resolve any changes in SPM fluidity which occur during aging as well as providing data on the structural topology of the membranes. Attempts will be made to correlate any changes in lipid composition with those found in fluidity. Alterations in membrane fluidity and composition can greatly change nerve activity. Membrane fluidity can alter both spontaneous and transmitter stiumulated nerve firing. In addition, the release and receptor mediated response to transmitter are affected by membrane viscosity. Changes in lipid composition and membrane fluidity do occur in peripheral tissues during aging. It is possible that changes in neuronal plasma membrane fluidity and composition are related to the mental dysfunction found in patients with Alzheimer's dementia.